In utero nicotine exposure causes persistent, gender‐dependant changes in locomotor activity and sensitivity to nicotine in C57Bl/6 mice

Abstract

Maternal cigarette smoking during pregnancy can result in a wide variety of adverse fetal outcomes, ranging from preterm delivery and low birth weight, to sudden infant death syndrome. In addition, in utero tobacco smoke exposure is associated with delayed or impaired neuropsychological development. Although the causative agent in tobacco smoke that leads to these aberrations is not known, some studies have concluded that nicotine may play an important role. Many studies using animal models of prenatal nicotine exposure have supported the hypothesis that nicotine may directly and/or indirectly cause impairments in fetal and neonatal development. However, in many of the animal studies nicotine has been administered acutely to naive dams, which could lead to significant fetal hypoxia; some routes of drug administration are also very stressful to pregnant dams, and changes in stress hormones could also create an unfavorable fetal environment. In this study, pregnant mice were exposed to chronic nicotine via the drinking solution; locomotor activity and sensitivity to nicotine were evaluated in the offspring. We have previously shown that oral nicotine administration produces behavioral and physiological changes that resemble those seen following other routes of nicotine administration. Although oral nicotine exposure did not significantly alter any aspect of the pregnancy, dams drinking a nicotine-containing solution consumed approximately 20% less volume, compared to saccharin controls. All animals were cross fostered to nicotine naïve lactating dams, immediately after birth. On PN40 and PN60, male mice exposed to in utero nicotine demonstrated significant locomotor hyperactivity in an open filed arena. Although female animals did not show any signs of hyperactivity, they did have a significant attenuation of their hypothermic response to acute nicotine challenge. These results suggest that oral nicotine delivery to pregnant mice causes persistent, gender-dependant changes in behavior and sensitivity to nicotine. This model may be very useful for future studies that try to more accurately define the windows of sensitivity for nicotine exposure and the possible underlying neurochemical mechanisms involved.

Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex

“…One of the issues regarding PNE model used in the present study is that pregnant mice drinking nicotine solution ingest approximately half of the liquids of those drinking vehicle (2% sucrose), the result being consistent with previous studies (Alkam et al, 2013b;Pauly et al, 2004). Accordingly, one might concern that PNE mice are malnourished (too little water during development), which could contribute to the observed effects in the offspring.…”

“…We believe, however, this is less likely because food was freely available during PNE from E14 to P0, and food intake and body weight of dam were not different between control and PNE groups. Further, there was no difference in the number and body weight of pups between control and PNE groups (Alkam et al, 2013b;Pauly et al, 2004). Nevertheless, to exclude the possible contribution of malnutrition in PNE-induced brain dysfunction in the offspring, further studies to analyze nutritional status of PNE mice would be required.…”

Cholinergic Modulation of Appetite-Related Synapses in Mouse Lateral Hypothalamic Slice

“…Pregnant females at 14 d after mating were given nicotine through the drinking water with sucrose (2%) and nicotine (200 g/ml) or with sucrose alone (control group) throughout the period of pregnancy and lactation. Based on other reports using this technique in mice, steady-state levels of nicotine achieved under these conditions are ϳ175 ng/ml in pup blood (Pauly et al, 2004).…”

Prenatal Nicotine Exposure Impairs Executive Control Signals in Medial Prefrontal Cortex

“…In addition to being an important issue in its own right, prenatal nicotine exposure has gained considerable traction as a suitable model for impulsive behavior as seen in ADHD. Exposing pregnant rodents to nicotine via drinking water produces offspring that bear striking resemblance to human ADHD both symptomatically and in treatment efficacy (Pauly et al, 2004;Peters and Tang, 1982;Peters et al, 1979;Schneider et al, 2010). This exposure has also been shown to have a genetic component in that pups of prenatally exposed pups also show behavioral impairments (Zhu et al, 2014).…”

“…The pups were weaned on postnatal day 21. We used male pups in all recording experiments because PNE has been shown to have more dramatic behavioral effects on males than females and ADHD-like diagnoses are more prevalent in males (Pauly et al, 2004;Peters and Tang, 1982;Romero and Chen, 2004;Vaglenova et al, 2004). Control and PNE pup weights were not significantly different from each other during first day of training (postnatal day 49; PNE = 271 g; control = 259 g; t-test; P = 0.56).…”